University of Texas M. D. Anderson Cancer Center, Houston, TX, United States.
Orlando Health, University of Florida Health Cancer Center, Orlando, FL, United States.
Oral Oncol. 2018 Jul;82:83-90. doi: 10.1016/j.oraloncology.2018.05.014. Epub 2018 May 19.
Cixutumumab (CIX) and cetuximab (CET) monoclonal antibodies block ligand-binding to insulin-like growth factor-1 receptor (IGF-1R) and epidermal growth factor receptor (EGFR) respectively. The objective of this study was to assess the efficacy of CIX alone or combined with CET in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients.
In this open-label phase II trial, 91 R/M HNSCC patients who progressed within 90 days of platinum-based chemotherapy, were randomized to CIX 10 mg/kg alone or with CET 500 mg/m every 2 weeks. Patients were stratified by prior CET use. The primary endpoint was median progression-free survival (PFS). Exploratory biomarker assessments included relevant markers on archival tumor and serial cytokine/angiogenic-factor profiles in blood.
Forty-seven patients were treated with CIX monotherapy and 44 with combination. The median PFS was 1.9 and 2.0 months and clinical benefit rate (complete or partial responses and stable disease) was 5.9% and 15.3%, respectively. There was no exacerbation of CET toxicity by concurrent CIX exposure. Higher tumor expression of IGF-1 was associated with improved PFS in the CIX + CET arm while increased p-EGFR expression correlated with shorter PFS in patients receiving single agent CIX. Higher serum baseline levels of IGF-1 and IGFBP-3 correlated with improved PFS and overall survival (OS) in the CIX arm. Neither regimen resulted in improved PFS or OS compared to historical data with CET alone.
The results of this study do not support the use of cixutumumab alone or with cetuximab in unselected patients with R/M HNSCC.
西妥昔单抗（CET）和西妥珠单抗（CIX）单克隆抗体分别阻断配体与胰岛素样生长因子-1 受体（IGF-1R）和表皮生长因子受体（EGFR）的结合。本研究的目的是评估 CIX 单药或联合 CET 治疗复发性/转移性头颈部鳞状细胞癌（R/M HNSCC）患者的疗效。
在这项开放标签的 II 期试验中，91 例在铂类化疗后 90 天内进展的 R/M HNSCC 患者按比例随机分为 CIX 10mg/kg 单药组或 CET 500mg/m 联合组，每 2 周一次。患者按是否使用过 CET 进行分层。主要终点是中位无进展生存期（PFS）。探索性生物标志物评估包括存档肿瘤的相关标志物和血液中细胞因子/血管生成因子的连续谱。
47 例患者接受 CIX 单药治疗，44 例患者接受联合治疗。CIX 单药组和联合组的中位 PFS 分别为 1.9 和 2.0 个月，临床获益率（完全或部分缓解和稳定疾病）分别为 5.9%和 15.3%。同时使用 CIX 并未加重 CET 毒性。CIX+CET 组中肿瘤 IGF-1 高表达与 PFS 延长相关，而 CIX 单药组中 p-EGFR 高表达与 PFS 缩短相关。CIX 组中血清基线 IGF-1 和 IGFBP-3 水平较高与 PFS 和总生存期（OS）延长相关。与单独使用 CET 相比，两种方案均未改善 PFS 或 OS。
本研究结果不支持在未经选择的 R/M HNSCC 患者中单独使用西妥昔单抗或联合西妥珠单抗。
